The role of maternal caffeine consumption in the pathogenesis of adverse pregnancy outcomes in controversial. Several studies have found that women who consume caffeine are at increased risk of spontaneous abortion and fetal growth retardation compared to non-users. However, other, equally well-done studies have found no harmful effects of caffeine consumption. In addition, several studies have reported that caffeine is harmful only among women who smoke. All previous studies of this question have relied on maternally-reported caffeine use; no studies have employed a biomarker for caffeine. This project will first validate the use of serum caffeine and its metabolites as a marker for caffeine intake, and will then study these serum markers as a risk factor for adverse pregnancy outcome. In the validation study, serum paraxanthine was determined to be an acceptable marker for caffeine intake. The main part of this project commenced in FY 97. In this portion, the serum concentration of paraxanthine, caffeine's primary metabolite, will be compared between 700 women experiencing a spontaneous abortion and 2800 women with live births who had serum drawn at the same time of pregnancy as the women with sponatneous loss. In addition, the association between reduced fetal growth and third-trimester paraxanthine serum concentrations will be evaluated among these 2800 women.